Motility Drugs

Functional gastrointestinal disorders (FGIDs) are heterogeneous group of gastrointestinal (GI) conditions characterized by chronic or recurrent GI symptoms without biochemical or structural abnormalities. Due to heterogenity of these disorders and complex pathophysiologic mechanisms, diagnosis and management still remain challenging. Current guidelines recommend stepwise and multimodality approaches, which include lifestyle changes to several classes of drugs (such as prokinetics, laxatives, antidepressants and central pain modulators). Prokinetics or “motility drugs” are compounds that stimulate gastrointestinal motility and, thereby, are clinically effective drugs for the treatment of FGIDs. According to the type of receptor they affect, they are divided into several groups: cholinergic agonists, dopamine (DA) receptor antagonists, motilin receptor agonists, ghrelin receptor agonist, 5-hydroxytryptamine (HT)4 receptor agonists, and other agents. The use of several prokinetic agents, such as cisapride and tegaserod, is associated with undesirable and serious cardiovascular side effects. This has led to restrictions on their use and withdrawal from the market by regulatory agencies which has discouraged drug development in this area. Despite that there is still a need for an effective and safe prokinetic. Drug development in this area is challenging, but a better understanding of physiological and pathophysiological mechanisms defines target receptors, leading to greater selectivity of prokinetic agents.